Palladium-catalyzed cross-coupling of α-diazocarbonyl compounds with arylboronic acids

Article abstract of DOI:10.1021/ja0782293

Pd(PPh₃)₄-catalyzed reaction between α-diazocarbonyl compounds and arylboronic acids leads to the formation of cross-coupling products in good yields. Copyright

Full text of DOI:10.1021/ja0782293

Published on Web 01/11/2008
Palladium-Catalyzed Cross-Coupling of r-Diazocarbonyl Compounds with
Arylboronic Acids
Cheng Peng, Yan Wang, and Jianbo Wang*
Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education, College of Chemistry, Peking UniVersity, Beijing 100871, China
Received October 27, 2007; E-mail: wangjb@pku.edu.cn
Table 1. Conditions on Pd-Catalyzed Reaction of 1 and 2aa
Suzuki-Miyaura reaction of aryl and vinyl halides or triflates
with organoboron reagents has developed into one of the most
important C-C bond-forming reactions.1,2 The mild and simple
reaction conditions, the availability of various boronic acids that
are normally nontoxic and stable, and easy workup and separation
of the products are some of the factors that are responsible for the
yield
(%)b
entry
catalyst (mol %)
solvent
base
T(
°
C)
time
increasing popularity of the Suzuki-Miyaura reaction. Our recent
interest is focused on the development of new methodology based
on palladium-catalyzed reactions of R-diazocarbonyl compounds.3
Although R-diazocarbonyl compounds have been extensively
applied as metal carbene precusors,4 the palladium-catalyzed
reaction has received only limited attentions.5-7 We have conceived
that the combination of Pd-carbene reaction with the transmetal-
lation of boronic acids would lead to novel transformations. Herein
we report a palladium-catalyzed cross-coupling reaction of aryl-
boronic acids with R-diazocarbonyl compounds. The reaction
affords R-aryl R,â-unsaturated carbonyl compounds, presumably
through migratory insertion reactions of palladium carbene inter-
mediate.
On the outset of this study, we have used methyl R-diazo-
propionate 1 and phenylboronic acid 2a as the substrates. When 1
and 2a were catalyzed with Pd(PPh3)4 in the presence of benzo-
quinone (BQ) and K2CO3, methyl 2-phenylacrylate 3a was isolated
in moderate yield (Table 1, entry 1). In the absence of the oxidant
BQ, the reaction gave trace 2-phenylacrylate 3a (entry 2). We went
on to screen other reaction parameters, such as temperature, solvent,
and base. It was found that the reaction proceeded more efficiently
at high-temperature (entry 3). The bases, such as K2CO3, Cs2CO3,
and Et3N afforded similar results, while i-Pr2NH was found the
most suitable base to promote the reaction with high yield (entries
6, 7). Polar solvent DCE could accelerate the reaction but led to
slightly low yield, while MeCN was found not favorable (entries
8, 9). Several other palladium catalysts were then examined. Pd-
(OAc)2, PdCl2(PPh3)2, and Pd(OAc)2/phosphine ligands all led to
lower yields of 3a (entries 10-14). Finally, for comparison the
reaction was carried out in the absence of Pd(PPh3)4. No product
3a could be detected.
1
2c
3
4
5
6
Pd(PPh3)4 (5)
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
K2CO3
K2CO3
K2CO3
Cs2CO3 80
Et3N 60
iPr2NH 80
60
60
80
30 min 53
Pd(PPh3)4 (5)
Pd(PPh3)4 (5)
Pd(PPh3)4(5)
Pd(PPh3)4 (5)
Pd(PPh3)4(2.5)
3 h
trace
30 min 64
30 min 45
30 min 50
15 min 74
15 min 82e,f
7d Pd(PPh3)4(2.5)
PhMe iPr2NH 80
DCE
iPr2NH 80
MeCN K2CO3 60
8d Pd(PPh3)4(2.5)
5 min
12 h
2 h
68
8
19
9
Pd(PPh3)4 (5)
10 d Pd(OAc)2 (2.5)
PhMe
PhMe
PhMe
iPr2NH 80
iPr2NH 80
iPr2NH 80
iPr2NH 80
11d PdCl2(PPh3)2 (2.5)
12d Pd2(dba)3(2.5)/PPh3(10)
30 min 27
15 min 41
13d Pd(OAc)2(2.5)/dppe(2.5) PhMe
1 h
3.5 h
15 h
34
51
0
14
Pd(OAc)2(5)/PPh3(20)
PhMe
PhMe
K2CO3
60
15 d none
iPr2NH 80
a The reaction was carried out with 1.0 equiv of 1 and 3.0 equiv of 2a.
b Isolated yield. c The reaction was carried out in the absence of BQ.
d Reaction run using 5 equiv of iPr2NH. e Biphenyl was isolated in 6% yield
based on 1. f When 2.0 equiv of 2a was used, 3a was isolated in 76% yield.
Table 2. Pd(PPh3)4-Catalyzed Reaction of 2a∼l with 1a
3, yield
(%)b
3, yield
(%)b
entry
2, Ar
entry
2, Ar
1
2
3
4
5
6
2a, C6H5
3a, 82
3b, 88
3c, 83
3d, 83
3e, 83
7
8
9
10
11
12
2g, p-CH3OC6H4 3g, 86
2b, o-CH3C6H4
2c, m-CH3C6H4
2d, p-CH3C6H4
2e, p-tBuC6H4
2h, m-NO2C6H4
2i, p-CHOC6H4
2j, p-ClC6H4
2k, p-BrC6H4
2l, 1-naphthyl
3h, 58
3i, 44
3j, 77
3k, 77
3l, 83
2f, 3,5-Me2C6H3 3f, 49
a The reaction was carried out with 1.0 equiv of 1 and 3.0 equiv of 2a∼l.
b Isolated yield.
A series of arylboronic acids were then subjected to the optimized
reaction conditions with methyl R-diazopropionate 1. The reaction
finished in 15 min with high efficiency and afforded methyl
R-arylacrylates in moderate to good yields (Table 2). The reaction
with o-, m-, and p-monoalkyl substituted arylboronic acids all
proceeded efficiently (entries 2∼5). The low yield in the reaction
with 3,5-dimethylsubstituted arylboronic acid was due to its low
solubility in toluene (entry 6). The reaction was found marginally
affected by electronic effects of the substituents of boronic acids.
The electron-donating group increased the reaction efficiency as
compared with electron-withdrawing groups (entries 7, 8, 9). It is
noteworthy that chloro and bromo substituents are tolerated in the
reaction conditions, which is advantageous for further transforma-
tions (entries 10, 11).
Next we studied the scope of the reaction with various R-dia-
zocarbonyl compounds (Table 3). A series of R-alkyl substituted
diazocarbonyl compounds were examined and all gave the cross-
coupling products in good yields. In the cases where trisubstituted
olefins were formed, the E and Z selectivity were low (entries 2,
3, 4). Notably, tetra-substituted olefin, which is difficult to access,
can be obtained in moderate yield (entry 5). The reaction also
worked well with R-diazoketones, including cyclic substrate (entries
6-9).
To elucidate the reaction mechanism of this novel palladium-
catalyzed cross-coupling reaction, we examined the possibility of
a process of 1,2-H shift of Pd-carbene intermediate,8 followed by
a Heck-Mizoroki-type reaction (eq 1).9 When methyl acrylate and
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J. AM. CHEM. SOC. 2008, 130, 1566-1567
10.1021/ja0782293 CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Pd(PPh3)4-Catalyzed Reaction of 4a∼i with 2aa
Scheme 1. Mechanistic Rationale
the aryl group to the carbenic carbon of the Pd-carbene gives
intermediate D. Finally, â-hydride elimination of D affords the
product and regenerates the Pd(0) species with the aid of base.
In summary, we have reported the first palladium-catalyzed cross-
coupling reaction of R-diazocarbonyl compounds with arylboronic
acids. It provides a novel access to R-aryl substituted R,â-
unsaturated carbonyl compounds. The reaction most likely proceeds
through a migratory insertion of the Pd-carbene species, a process
that has attracted attention only very recently.5c,e,6,7a,10
Acknowledgment. The project is supported by NSFC (No.
20572002, 20521202, 20772003) and the MOE of China (Cheung
Kong Scholars Program). We thank our colleague Dr. Zhangjie Shi
for stimulating and insightful conversation.
Supporting Information Available: Experiment procedure and
characterization data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) For the seminal publications, see: (a) Miyaura, N.; Yamada, K.; Suzuki,
A. Tetrahedron Lett. 1979, 20, 3437. (b) Miyaura, N.; Suzuki, A. J. Chem.
Soc., Chem. Commun. 1979, 866.
(2) For reviews, see: (a) Suzuki, A. Acc. Chem. Res. 1982, 15, 178. (b)
Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (c) Miyaura, N. J.
Organomet. Chem. 2002, 653, 54. (d) Miyaura, N. In Advances in Metal-
Organic Chemistry; Liebeskind, L. S., Ed.; JAI: London, 1998; Vol. 6,
pp 187. (e) Suzuki, A. In Metal-Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998; Chapter
2. (f) Stanforth, S. P. Tetrahedron 1998, 54, 263. (g) Suzuki, A. J.
Organomet. Chem. 1999, 576, 147. (h) Miyaura, N. Top. Curr. Chem.
2002, 219, 11. (i) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002,
41, 4176. (j) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem.,
Int. Ed. 2005, 44, 4442.
a Reaction conditions: 4a-i (1 equiv), 2a (3 equiv). b Isolated yield.
1
c Ratio determined by H NMR of the crude product.
phenylboronic acid were subjected to the identical reaction condi-
tions, methyl cinnamate was isolated in low yield, and no 3a could
be detected (eq 2). Therefore, this pathway can be ruled out.
(3) Peng, C.; Cheng, J.; Wang, J. J. Am Chem. Soc. 2007, 129, 8708.
(4) For comprehensive reviews, see: (a) Doyle, M. P.; McKervey, M. A.;
Ye, T. Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds; Wiley-Interscience: New York, 1998. (b) Ye, T.; McKervey,
M. A. Chem. ReV. 1994, 94, 1091.
(5) (a) Anciaux, A. J.; Hubert, A. J.; Noels, A. F.; Petiniot, N.; Teyssie´, P. J.
Org. Chem. 1980, 45, 695. (b) Denmark, S. E.; Stavenger, R. A.; Faucher,
A.-M.; Edwards, J. P. J. Org. Chem. 1997, 62, 3375. (c) Greenman, K.
L.; Carter, D. S.; Van Vranken, D. L. Tetrahedron 2001, 57, 5219. (d)
Bro¨ring, M.; Brandt, C. D.; Stellwag, S. Chem. Commun. 2003, 2344. (e)
Greenman, K. L.; Van Vranken, D. L. Tetrahedron 2005, 61, 6438.
Very recently, Van Vranken and co-workers have reported
palladium-catalyzed three-component coupling of vinyl halides,
trimethylsilyldiazomethane, and amines to generate allylamines.6
Barluenga and co-workers have reported a palladium-catalyzed
cross-coupling reaction of N-tosylhydrazones and aryl halides, in
which diazo compounds are generated in situ.7a In both reactions,
palladium carbene species are suggested as the key intermediates,
from which migratory insertion reactions occur.
On the basis of these results, we propose a possible mechanism
as shown in Scheme 1. The reaction is initiated by the oxidation
of Pd(0)Ln by BQ to generate Pd(II) intermediate A. Then
transmetallation with arylboronic acid takes place to give intermedi-
ate B. The reaction of R-diazocarbonyl compound with palladium
complex B would produce Pd complex C. Migratory insertion of
(6) Devine, S. K. J.; Van Vranken, D. L. Org. Lett. 2007, 9, 2047.
(7) (a) Barluenga, J.; Moriel, P.; Valde´s, C.; Aznar, F. Angew. Chem., Int.
Ed. 2007, 46, 5587. (b) We have found that Pd(0)-catalyzed coupling of
1 with iodobenzene also occurs (see Supporting Information).
(8) For a recent report on 1,2-H shift of Rh(II) carbene, see: Xiao, F.; Wang,
J. J. Org. Chem. 2006, 71, 5789.
(9) (a) Du, X.; Suguro, M.; Hirabayashi, K.; Mori, A. Org. Lett. 2001, 3,
3313. (b) Enquist, P.-A.; Lindh, J.; Nilsson, P.; Larhed, M. Green Chem.
2006, 8, 338. (c) Yoo, K. S.; Yoon, C. H.; Jung, K. W. J. Am. Chem.
Soc. 2006, 128, 16384.
(10) (a) Danopoulos, A. A.; Tsoureas, N.; Green, J. C.; Hursthouse, M. B.
Chem. Commun. 2003, 756. (b) Albe´niz, A. C.; Espinet, P.; Manrique,
R.; Pe´rez-Mateo, A. Chem. Eur. J. 2005, 11, 1565. (c) Lo´pez-Alberca,
M. P.; Manchen˜o, M. J.; Ferna´ndez, I.; Go´mez-Gallego, M.; Sierra, M.
A.; Torres, R. Org. Lett. 2007, 9, 1757.
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